Rhenium-188 (Re-188) is one of the most attractive radioisotopes for radioimmunotherapy since it can be obtained from a tungsten-188/rhenium-188 generator system. There is currently widespread interest in Re-188 for therapeutic applications. Re-188 has a half-life of 16.9 hours and decays by .beta. emission with an average energy of 764 keV. Re-188 also emits a gamma photon with an energy of 155 keV in about 15% abundance. The emission of gamma photons is an important aspect of the decay scheme since they can be efficiently detected with the state-of-the-art, widely used, gamma cameras. Determination of the biodistribution with a gamma camera can provide important information on organ distribution. In addition, the biodistribution and kinetic data can be subsequently used for absorbed radiation dose estimates, which is important in determining the effectiveness, safety and efficacy in using Re-188 labeled agents for therapy.
Rhenium is an analogue of technetium (Tc) in chemical behavior, and recent advances in chemistry of Tc, with focus on the biomedical application of Tc-99m, could in principal be extended to Re-188. As an example of other generator-produced radionuclides used for therapy, yttrium-90 (Y-90) is currently broadly used for antitumor therapy and other medical applications, but does not emit photons which can be imaged, as does Re-188. Tumor therapy with Re-188 labeled antibodies or Re-188 labeled sulfur colloids for treatment of rheumatoid arthritis of the knee joints and other large synovial joints are two major applications of this radioisotope.
Re-188 is obtained in carrier-free state from decay of W-188, (t.sub.1/2 =69.4 d) in a generator system. The parent isotope, W-188 is produced by W-186 double neutron capture in a nuclear reactor such as is available from the Oak Ridge National Laboratory (ORNL), Oak Ridge, Tenn.
An alumina based W-188/Re-188 generator system was developed at ORNL, and produced Re-188 as a salt. The generator system generally operates as follows. W-188 is loaded onto an alumina column as tungstic acid, and Re-188 is eluted from column with normal saline (0.155 N NaCl). The required bolus volume for the quantitative elution of Re-188 depends on the size of the column which in turn is inversely proportional to the specify activity of W-188. In a typical 1.times.3.5 cm column filled with 100 to 200 mesh activated alumina loaded with about 30 mg of W (the mass of W containing 100 mCi of W-188 with specific activity of 3.5 mCi/mg) quantitative elution of the Re-188 daughter is achieved with about 20 ml of eluent. Breakthrough of the W-188 parent is generally less than 1.times.10.sup.-4 %.
Another type of W-188/Re-188 generator system recently described is a "Gel Type" system developed at the University of Missouri [G. J. Ehrhardt et al., Proceedings of the 34th annular meeting, Society of Nuclear Medicine, 1987, Abstract No. 416], which involves precipitation of low specific activity W-188 with a zirconium salt to form a gel which is then packed in a column and eluted with saline.
Earlier systems include a zirconium oxide column [Lewis et al., J. Nucl. Med., 7, 804-805 (1966) and Hayes, et al., ORAU Medical Division Research Report, ORAU 101 (1966)], and phosphotungstate on alumina [Mikheev et al., U.S.S.R., (1972]. These methods and systems produce Re-188 in the form of a perrhenate. In other system, tungsten fluoride was absorbed on an anion exchanger and eluted with perchloric acid [Blachot et al., Int. J. Applied Radiation and Isotopes, 20, 467-470 (1969)]. That system produced perrhenic acid, but the presence of perchloric acid may render the product impractical for most biological radiolabeling procedures.
Methods for removing the cations in generator column produced Re-188 solutions is important for volume reduction and for radiolabeling procedures. Methods for overcoming the presence of high levels of cations is carrier-free Re-188 solutions is also needed for maximum flexibility for protein labeling and the like. Since Re-188 in the form of perrhenic acid can be used for radiolabeling various ligands, method and apparatus are needed for removing alkali metals from the eluent and provide a concentrated solution of Re-188 perrhenic acid in HC1 or HNO.sub.3.